Biomedical subjects
Publications and source records attributed to P Schweizer.
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Since 1990, we have been conducting ambulatory pediatric surgery in an unit established solely for this purpose, supported by a team of kindergarten teachers, pediatric nurses, anesthesiologists and pediatric surgeons. This prospective investigation includes all ambulatory pediatric operations performed in our department from 1990 to 1995. In this time 3665 infants and children between the ages of 6 weeks and 18 years underwent an ambulatory operation. The ratio male to female was 4.1 to 1. The series consists of 1400 inguinal hernias, 722 inguinal testes, 191 hydroceles/funiculoceles, 75 umbilical hernias, 667 phimoses, 70 meatotomies, 59 hemangiomas, 217 endoscopies and 264 other surgical procedures. Postoperative complications defined as secondary hemorrhage, fever, obvious vomiting, urine retention and laryngospasm upon terminating anesthesia accompanied by subsequent vomiting occurred in 59 (1.6%) of all infants and children. Wound infections were seen in 0.48% (17/3517) of all patients. The recurrence rate for inguinal hernias were 0.79% and 1.12% for inguinal testes. Our experience enables us to summarize that a variety of pediatric operations can be performed today as ambulatory procedures. Nevertheless one must be prepared for the occurrence of complications and always have capacities free for inpatient care where adequate observation and treatment are available. Further improvement is necessary in quality management. In the last 20 years only a few data have been published about recurrence rates after pediatric ambulatory operations for inguinal hernias and inguinal testes. Therefore we started a prospective long- term study.
The surgery of biliary ducts and malignant liver tumors is formulated illustratively in guidelines in order to assist the physician as well as the uninformed patient in their orientation concerning diagnostic, therapeutic and prognostic questions. Special attention is paid to diagnostics, which is based on both rational and empirical verified arguments. Moreover, the examples presented in this study show that guidelines can only be formulated if extensive verified knowledge exists; for rare diseases and those about which little is yet known guidelines cannot (yet) be formulated.
The volumes of the external and internal anal-sphincter muscles, determined by three-dimensional (3d) endosonography, are linear to each other and to the body-height and body-surface ratios in normal children. In patients with an operation of the sphincter muscles, the reduced volume of the external sphincter system permits a differentiation of incontinent children; the volume of the internal sphincter muscles, however, doesn't give a significant difference nor does the muscle-thickness. An acceptable estimation of the sphincter muscles volume can be made with conventional endosonography by planimetry of the muscle tissue in four representative axial cut-planes and by measuring of the sphincter-length.
After an introduction, three selected contributions to the 10th Course on Radiation Protection held at the University Hospital of Basel are presented. The principles of radiation protection and new Swiss legislation are discussed as the basis for radiological protection. Ways are proposed of reducing radiation exposure while optimizing the X-ray picture with a minimum dose to patient and personnel. Radiation effects from low doses. From the beginning, life on this planet has been exposed to ionizing radiation from natural sources. For about one century additional irradiation has reached us from man-made sources as well. In Switzerland the overall annual radiation exposure from ambient and man-made sources amounts to about 4 mSv. The terrestrial and cosmic radiation and natural radionuclids in the body cause about 1.17 mSv (29%). As much as 1.6 mSv (40%) results from exposure to radon and its progenies, primarily inside homes. Medical applications contribute approximately 1 mSv (26%) to the annual radiation exposure and releases from atomic weapons, nuclear facilities and miscellaneous industrial operations yield less than 0.12 mSv (< 5%) to the annual dose. Observations of detrimental radiation effects from intermediate to high doses are challenged by observations of biopositive adaptive responses and hormesis following low dose exposure. The important question, whether cellular adaptive response or hormesis could cause beneficial effects to the human organism that would outweigh the detrimental effects attributed to low radiation doses, remains to be resolved. Whether radiation exerts a detrimental, inhibitory, modifying or even beneficial effect is likely to result from identical molecular lesions but to depend upon their quantity, localization and time scale of initiation, as well as the specific responsiveness of the cellular systems involved. For matters of radiation protection the bionegative radiation effects are classified as deterministic effects or stochastic effects respectively. The various histopathological reactions of tissues and organs following localized tissue irradiation, and the radiation syndromes following total body irradiation, constitute the deterministic effects. There will be a threshold below which deterministic effects do not appear and spontaneous incidences are not known. For low dose risk considerations deterministic effects are of no significance. Genetic effects and carcinogenesis are said to be stochastic effects. Characteristically the probability of stochastic effects increases with dose but the severity of the effects is independent of the dose. The shape of the dose-response relationship at intermediate to high dose levels is linear-quadratic. For exposure to low doses the response becomes linear, as is to be expected for a linear-quadratic function at low dose. No threshold is assumed for stochastic effects. The estimate of probability of fatal cancer by the ICRP is 4 x 10(-2) per Sv for the working population and 5 x 10(-2) per Sv for the total population. Their estimate of probability of serious hereditary disorders within the first two generations is 1 x 10(-2) per Sv. The highest probability coefficient is attributed to mental retardation following exposure in utero. Within the sensitive period at 8-15 weeks of gestation, a risk probability of 40 x 10(-2) per Sv is assumed but a threshold at 0.1 Sv is not excluded. Conclusions drawn from experiments, clinical observations and epidemiological studies following intermediate to high radiation exposures attribute a mutagenic and carcinogenic competence to all radiation doses. Microdosimetric considerations support this assumption. This conclusion cannot be confirmed experimentally nor by epidemiological studies of populations living under different conditions from natural sources of radiation. Nevertheless, a change in the present restrictive radiation protection policy does not yet appear appropriate.
Molecular biological markers that influence prognosis should be considered in the optimization of therapy for disseminated forms of neuroblastoma. Some of these markers include: N-myc amplification, deletion of 1p36, ploidy, and trk expression. Neuroblastoma without N-myc amplification and high trk expression show a favorable outcome and would enable a more gentle chemotherapy treatment. Neuroblastomas with N-myc amplification and lack of trk expression behave extremely unfavorably and require an even more intensive treatment.
We report on nine children, 9 to 17 years of age, with papillary carcinoma of the thyroid, whereby eight of them had lymph node metastases, and four had diffuse pulmonary metastases. After total thyroidectomy and up to four cycles of radioiodine treatment, as well as surgical resection of metastases negative to radioactive iodine uptake, there was no evidence of relapsing disease in any of the children. Hence, taking into consideration and optimal tumor patient follow-up and the improvement of the long-term prognosis, we recommended total thyroidectomy, also for encapsulated, well-differentiated thyroid carcinomas.
The thioether lysophospholipid BM 41.440 proved to be toxic against cells of two neuroblastoma cell lines in a dose- and time-dependent manner. The ID50 estimated in three different in vitro test systems declined from about 10 micrograms/ml after 24 h to 1 microgram/ml after a 1-week treatment of the neuroblastoma cells. These values are comparable to the ID50 found for neoplastic cells derived from other tissues. In comparison, hematopoietic progenitor cells (granulocyte/monocyte-colony-forming units) proved to be less sensitive to short-term treatment with BM 41.440. After long exposure to this drug the selectivity towards neuroblastoma cells decreased. This observation makes it unlikely that BM 41.440 can be used for treatment of neoplasia such as neuroblastoma, because only short-term treatment is acceptable considering the high bone marrow toxicity.
Clinical and procedural experience using transjugylar intrahepatic portosystemic shunt (TIPS) on 7 children with recurrent hemorrhage of esophageal varices is reported. Recurrent hemorrhage from esophageal varices following repeated paravasal sclerosing of the varices as well as severe-grade hypersplenism are proposed as the indication for its use. The technical details of TIPS, observed and possible early and late complications, the demand for a decrease in the portosystemic pressure gradient to less than 15 mmHg and the influence of TIPS on improvement of the varices, hypersplenism and the frequently observed malabsorption are described.
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The development of plant in vitro transcription systems transcribing faithfully and efficiently from a broad range of plant nuclear promoters has remained a challenge. We examined the nucleotide sequence requirements for faithful and efficient transcription in a wheat germ chromatin extract (Yamazaki et al., Plant Mol Biol Rep 8: 114-123). The wheat germ chromatin extract was tested with a series of chimeric promoter constructs containing plant promoter sequences upstream from the TATA box, TATA boxes, and cap-site sequences (from -10 to +14, relative to the major in vivo initiation site) in different combinations. The plant extract transcribed faithfully from several chimeric promoters containing the capsite sequence of the parsley chalcone synthase promoter. The transcription was sensitive to the RNA polymerase II-specific inhibitor alpha-amanitin and was only dependent on the chalcone synthase cap-site sequence which therefore fulfils the operational criteria for a plant initiator element. Mutations of the putative chalcone synthase initiator element defined a core sequence '5'TAACAAC' around the initiation site that was necessary for efficient transcription in vitro. In contrast to the extract, purified wheat germ RNA polymerase II showed no preference for transcription from the major chalcone synthase in vivo initiation site.
Anorectal manometry was performed in a series of 8 children where NID was histochemically confirmed or suspected. The results were transferred to a electromanometric score theoretically worked out previously. Clinical symptoms as well as histological and manometric findings have been compared concerning the meaningfulness of the electromanometric score in the diagnosis of NID. It was impossible to make a statistical statement due to the small number of patients we examined. It seems, however, that certain electromanometric parameters in NID appear regularly which, when combined in a score, make manometric diagnosis of NID sufficiently reliable.
As an alternative to soluble plant transcription systems, we examined the reinitiation capacity of isolated parsley nuclei. Nuclear chalcone synthase in vitro transcripts were affinity-labelled with gamma-thio-ATP, gamma-thio-GTP or beta-thio-ATP, and purified by chromatography on a mercury Sepharose affinity column. Primer extension and subsequent PCR amplification of these in vitro transcripts revealed gamma-thio-ATP-dependent, but no beta-thio-ATP-dependent, signals, although affinity labelling of overall in vitro transcripts still occurred with beta-thio-ATP. We conclude that the described plant nuclei reinitiated transcription non-specifically and that post-transcriptional transfer of the gamma-thio affinity label severely interfered with the detection of reinitiated transcripts.
Retrospectively evaluated clinical, radiological and anatomical findings of 46 patients with tubular or cystic dilated choledochal ducts indicate the following conclusion: Pathological stricture of the sphincter of Oddi system, including a hypertrophic and spastic portion of the sphincter choledochus inferior, called "narrow segment", raises the pressure in the choledochal duct to pathological levels and consequently causes a dilatation of the duct during a specific embryonic phase. Such a pathological sphincter of Oddi system develops if a long common channel persists as the result of a disturbance in the development of the distal choledochal and pancreatic duct. This statement contradicts the classical conception which assumes that a reflux of pancreatic juice into the choledochal duct causes ductal dilatation. Authors who are in favor of this conception propose that pancreatic juice causes weakness of the ductal wall, which may be dilated in the embryonic period. However, the findings of the series evaluated here show that dilatation of the duct may also originate without any reflux of pancreatic juice into the choledochal duct if a "narrow segment" exists above the junction of the pancreatic and choledochal ducts. For this reason, pancreatic juice reflux cannot be the condition sine qua non in the development of choledochal duct dilatation. Similarly the pathologic junction angulation can only be an optional factor in this autogenetic anomaly. With regard to a pathological sphincter of Oddi system the question arises whether a partial or complete myotomy of the muscular sphincter may be able to remedy the dilatation and avoid resection of the choledochal duct.(ABSTRACT TRUNCATED AT 250 WORDS)
In recent years hepatoportoenterostomy according to Kasai undoubtedly was the only successful therapy for extrahepatic biliary atresia. Since liver-transplantation becomes more successful than previously, the question arises if the Kasai procedure is still justified. From this point of view a prospective study was started based on the following findings in 15 EHBA-children after hepatoportoenterostomy compared to those in 15 patients without the Kasai procedure: the survival rate at the end of two years of life; the development of ascites until the end of the first year of life; the weight and length percentiles at the end of the first year of life; and the activity of serum cholinesterase. In order to calculate significant differences in weight and length percentiles, the exact Fisher test was used. Serum cholinesterase activities of both the above mentioned groups were compared with each other, as well as with the normal values of a third group of 50 healthy children, by analyzing variances and then comparing one by one with adjustment for multiple comparisons. There was a significant difference between the operated and not-operated group, and in addition between the non-operated and the healthy group. In contrast, no significant difference was detected between the operated and the healthy group. These differences were best demonstrated by the findings of weight and length percentiles and the activity of serum cholinesterase. From this we conclude sofar hepatoportoenterostomy undoubtedly is standard procedure in the treatment of EHGA. However, if the Kasai procedure fails or the liver disease progresses to a greater extent, liver transplantation will become the method of choice.
To rationally discuss the "need for preoperative laboratory investigations prior to performing an operation that can be pre-planned", two questions must be considered: 1. What kind of complications were encountered during or after 25,872 anesthesias performed in a 20-year period? 2. What kind of diseases were recognized only postoperatively which apparently could not be diagnosed preoperatively via case history and clinical examination? The results of these analyses are tabulated and assessed. It could be shown that the case history and the clinical examination of the patient on the day of surgery rank before all laboratory tests. With regard to peroperative respiratory disturbances it could be proven that children within the first trimester are particularly susceptible to such alterations. Furthermore, it could be demonstrated that within this group premature babies are more susceptible to this kind of complication than babies born at date. With regard to the incidence of preoperative respiratory disturbances in children with or without infection of the upper respiratory tract, it was shown that children without such symptoms who had however undergone an infection three to four weeks before the operation, were more susceptible to peroperative respiratory disturbances than children without any infection or even children suffering from an acute infection. Taking the physiological Hb decrease at the end of the first trimester as an example, questions on the optimal date for surgery are discussed. Preoperative handling is discussed on the basis of the blood glucose level of 500 children after a fasting period of 3-4 hours.
In order to define diagnostic and therapeutic guidelines from a paediatric surgical point of view, clinical, laboratory chemical and intraoperative findings from 52 children with necrotising enterocolitis (NEC) were evaluated and correlated with fatality. This analysis produced the following results: 1. The fatality rate for patients with "proven" NEC (n = 28) was 3 = 9%. All 3 of these children who died were so-called "high risk" patients. The fatality rate for patients with "advanced" NEC (n = 24) with intestinal perforation was 6 = 25%. Five of these children who died were so-called "high risk" patients. These 2 patient groups are comparable because the concepts of surgical indication and timing were identical, the technical conditions for surgery were the same, a standardised surgical procedure was employed, and the distribution pattern and extent of intestinal damage were consistent, except for the intestinal perforation in the second group. In addition, the proportion of "high risk" patients was approximately the same in both groups. Therefore, the 2 groups differed only in the attribute of intestinal perforation. Accordingly, the results of comparison cannot be considered to be statistically significant, yet they do indicate a prognostic tendency: Children who cannot receive surgery until after the occurrence of intestinal perforation have a poorer prognosis. 2. The highly indicative diagnostic criterion for proof of developing intestinal gangrene is puncture of the abdominal cavity, enabling detection of migratory peritonitis. 3. With regard to fatality, a comparison of various surgical procedures confirms the special importance of an enterostoma over primary anastomosis. Exceptions only serve to prove the rule here as well.
"Extrahepatic bile duct atresias" must be classified into 4 histopathological groups according to their characteristic numerical, metrical and morphological alterations of interlobular bile ducts. A prospective study based on an observation period of 5 and more years included 43 patients with "extrahepatic biliary atresia". It showed that prognosis generally depends on 3 factors: the duration of cholestasis, the prehilar structure of the bile ducts, and the histopathologically defined features of the interlobular bile ducts. The total diameter of all the prehilar bile duct structures is unmistakably the most dominant of all findings. A total diameter of more than 400 microns indicates a favourable prognostic subtype, while a total diameter of less than 400 microns indicates an unfavourable prognostic subtype. However, even if the prognostically favourable type of findings is present, the actual prognosis is finally determined by the histopathological features of the interlobular bile ducts. Therefore, these 4 characteristic groups must be taken into consideration when rationally evaluating the prognosis.